Chronic sleep loss affects millions of Americans. Short sleep schedules are associated with increased risk of weight gain, obesity, diabetes, the metabolic syndrome, and accidents. It is unknown if the common and self- selected behavior of weekend recovery sleep helps to protect against the health and safety effects of sleep loss. Furthermore, we do not fully understand the physiological and behavioral mechanisms that contribute to the negative health effects associated with sleep loss nor do we fully understand the time course of how quickly changes in some of these physiological systems occur. Therefore, we have designed a randomized 14-16 day in- lab Clinical and Translational Research Center (CTRC) study that uses whole room calorimetric, hyperinsulinemic/euglycemic clamps and safety sensitive cognitive tests to address these critical deficiencies in our knowledge. The stage for the proposed research was set by our NIH ARRA grant "Heath and Safety Consequences of Sleep Loss" and our proposed project is a continuation of this research effort. The project addresses several themes outlined in NIH PA NUMBER: PA-10-152 "Diet Composition and Energy Balance" by testing the following specific hypotheses: i) chronic sleep loss will lead to positive energy balance-a physiological state contributing to weight gain and weekend recovery sleep will restore energy balance to near baseline levels;ii) chronic sleep loss will impair insulin sensitivity and weekend recovery sleep will restore insulin sensitivity to near baseline levels;iii) chronic sleep loss will impair cognition and weekend recovery sleep will restore performance levels to near baseline. This research effort is responsive to PA-10-152 by assessing effects of sleep deprivation on macronutrient consumption and effects of dietary composition on physiological responses to sleep loss. The proposed project also meets the following highest recommendations for future research in the NIH National Center on Sleep Disorders Research (NCSDR) 2003 plan: i) enhance understanding of the impact of reduced or restricted sleep on behavior, and neurobiologic and physiologic functions;and ii) mechanisms underlying aspects of chronic sleep deprivation on non-neural systems. PUBLIC HEALTH RELEVANCE: Chronic sleep loss affects millions of people each year representing an important public health issue. This project will address key deficiencies in our knowledge regarding mechanisms underlying the health and safety consequences of sleep loss and the ability of weekend recovery sleep in mitigating these consequences. We anticipate that or findings will improve our understanding of how sleep loss contributes to disease processes involved in weight gain, obesity, diabetes, and the metabolic syndrome and how sleep loss increases accident risk and reduces work and school productivity. Importantly, we expect that our findings will highlight the health and safety benefits of weekend recovery sleep.